Synthesis of Unsymmetrical β-Enamino Ketones

Article abstract of DOI:10.1055/s-2003-41067

A convenient procedure for modification of β-enaminones by α-C-acylation and subsequent acidic cleavage is described. The unsymmetrical β-enamino ketones obtained in this way could be hydrolyzed to provide an entry towards various unsymmetrical 1,3-diketones.

Full text of DOI:10.1055/s-2003-41067

PAPER
2221
Synthesis of Unsymmetrical -Enamino Ketones
Synthesisof
U
nsym
t
metri
a
cal -Enam
n
ino Ketonesas P. Venkov,*1 Plamen A. Angelov
Department of Organic Chemistry, University of Plovdiv, 24 ‘Tsar Asen’ str., 4000 Plovdiv, Bulgaria
E-mail: angelov@argon.acad.bg
Received 21 May 2003; revised 1 July 2003
This paper is dedicated to the memory of Professor Atanas Venkov.
of the NH signal (from 8.63–10.92 to 11.36–12.55 ppm).
For C-acylated enamino amides as 2n–p, the methyl (R1)
signal at 1.70–1.80 ppm is unusually broad and the amide
NH appears as two signals at 7.48–7.76 and 11.39–11.80
ppm, which is most likely due to a rotameric interconver-
sion.
Abstract: A convenient procedure for modification of -enamino-
nes by -C-acylation and subsequent acidic cleavage is described.
The unsymmetrical -enamino ketones obtained in this way could
be hydrolyzed to provide an entry towards various unsymmetrical
1,3-diketones.
Key words: enaminones, C-acylation, cleavage, 1,3-diketones, un-
symmetrical
The acylation of enaminones 1 to 2 was carried out in
CH2Cl2 at room temperature in the presence of Et3N. In
general, improved yields of C-acylated enaminones 2
were obtained, when the reactions were carried out with
an excess of acyl chloride and Et3N (e.g. twofold excess).
The yields of 2 varied from excellent to moderate, de-
pending on the nature of the substituents R1, R2, and R3
(Table 1). The best yields of 2 were obtained when R2 is a
good electron-donating group (Table 1, 2d–g). When R2
in 1 is a methyl group, good yields of 2 were obtained only
with strongly electrophilic acyl chlorides such as trichlo-
roacetylchloride (Table 1, 2h–m). The nucleophilicity of
the -carbon in 1 deteriorates strongly when R2 is an elec-
tron-withdrawing group, such as trichloromethyl group,
and no acylation takes place under the investigated condi-
tions.
The versatility of -enaminones as synthetic intermedi-
ates has drawn considerable attention to this class of com-
pounds. Their synthetic applications as well as the
methods for preparation have been extensively re-
viewed.2a–d Even though numerous syntheses of enamino-
nes have been reported, the most common way for their
preparation remains the condensation between an amine
and a 1,3-dicarbonyl compound. This procedure, howev-
er, has two general drawbacks:
a) It is not always successful with unsymmetrical 1,3-
diketones, because it often lacks the desired regioselectiv-
ity and in such cases other methods, like acylation of lithi-
ated imines,3a,b must be used.
Our investigations on the behavior of the C-acylated prod-
ucts 2 in acidic media such as in TFA, phosphoric acid,7
or H2SO4 showed cleavage of the R2CO group affording
enaminones 3 (Scheme 1, Table 1, 3d–p). We found that
this transformation was possible if R2 is a markedly better
electron-donating group than R3. Treatment of 2h–m with
TFA at room temperature for 1 hour leads to the corre-
sponding new enaminones 3h–m with excellent yields
(Table 1). When R2 and R3 in 2 have similar electron do-
nating properties, the cleavage of acyl group was not pos-
sible under the same reaction conditions (Table 1, 2a–c).
Mixtures of products were obtained from 2a–c at elevated
temperatures. When R2 is an amino group the cleavage
was carried out for 1 hour in refluxing TFA (Table 1, 3e–
g) or for 30 minutes in H3PO4 at 65 °C (Table 1, 3d, n–p).
b) Many 1,3-diketones are not readily available.
In this report we outline a simple synthetic procedure that
has the potential to overcome the above-mentioned prob-
lems.
In a recent communication we have reported a cyclization
of 2-(3,4-dimethoxyphenyl)ethylamine derived -enami-
nones (Table 1, 1a–h) to 1,1-disubstituted tetrahydroiso-
quinolines.4 In an attempt to facilitate the cyclization
reactions, we tried to obtain N-acyl derivatives of the
enaminones, as this approach has been reported earlier to
be successful for similar types of enaminones.5a,b Howev-
er, the acylation of compounds 1a–h in the presence of
bases like Et3N or pyridine led to -C-acylated products
(Scheme 1, Table 1, 2a–h). C-Acylation of enaminones
with acyl chlorides is reported in the literature only inci-
dentally,6a–c so we extended the reaction to different types
of enaminones. The additional experiments (Table 1, 2i–
p) showed that the nature of the studied substituents R–R3
The leaving group properties of the carbamoyl groups in
the above examples depend on the substitution pattern of
the amide nitrogen, as the results for entries 3e–g show
(Table 1). In the case of tertiary nitrogen, as in 2g, the
product 3g was obtained only in trace amounts.
1
does not significantly change the reactivity pattern. H
NMR spectra of 2 indicated the disappearance of the vinyl
proton from 1 (4.30–5.10 ppm) as well as downfield shift
Even though there was partial hydrolysis of some of the
enaminones 3 during the aqueous work up (Table 1, 3d–
f), the others were isolated in very good yields. All of the
isolated enaminones 3 were found to exist in their Z-con-
figuration stabilized by an intramolecular H-bond, which
SYNTHESIS 2003, No. 14, pp 2221–2225
0
2.
1
0
.
2
0
0
3
Advanced online publication: 24.09.2003
DOI: 10.1055/s-2003-41067; Art ID: Z06503SS.pdf
© Georg Thieme Verlag Stuttgart · New York

2222
A. P. Venkov, P. A. Angelov
PAPER
R
R
R
NH
O
NH
O
O
NH
O
OH
O
R3COCl
Et3N
H+
H3O+
R1
R2
R1
R2
R1
R3
R1
R3
R3
1
2
3
4
Scheme 1 For details see Table 1 and the experimental part.
Table 1 Compounds 2 and 3 Prepared via Scheme 1
Compd R
R1
R2
R3
2
3
Time (h) Yield (%) Conditions
Yield (%)a
a
b
c
d
e
f
3,4-(CH3O)2C6H3CH2CH2
CH3
CH3
C6H5
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CCl3
CCl3
CCl3
CCl3
CCl3
CCl3
24
4
50b
75
55b
80b
80
85
82
85
80
85
53
73
79
60
73
60
–
–
–
–
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
3,4-(CH3O)2C6H3CH2CH2
C6H5CH2CH2
OEt
–
OEt
4
–
NHC6H5
NH2
4
H3PO4, 65 °C, 30 min
TFA, reflux, 1 h
TFA, reflux, 1 h
TFA, reflux, 1 h
TFA, r.t., 1 h
68
55
75
3
2
NHC6H5
NEt2
2
g
h
i
2
CH3
48
48
48
8
96
92
94
91
93
95
86
95
90
CH3
TFA, r.t., 1 h
j
3,4-(CH3O)2C6H3CH2
C6H5CH2
CH3
TFA, r.t., 1 h
k
l
CH3
TFA, r.t., 1 h
CH3CH2CH2
CH3
48
48
24
24
24
TFA, r.t., 1 h
m
n
o
p
Et
CH3
TFA, r.t., 1 h
Et
NHC6H5
NHC6H5
NHC6H5
C6H5
H3PO4, 65 °C, 30 min
H3PO4, 65 °C, 30 min
H3PO4, 65 °C, 1 h
Et
4-NO2-C6H4
2,4-Cl2-C6H3
Et
a Based on 2.
b With two equiv R3COCl and Et3N.
shows that E–Z isomerization takes place at some stage of that the configuration of the enaminones has a profound
the reaction. The configurational assignment was made on effect on the position of this signal.8a,b
the basis of the position of the NH signal in the 1H NMR
spectra (10.70–11.57 ppm). It has been well established
Acidic hydrolysis of the obtained enamino ketones 3
could be useful for the preparation of unsymmetrical 1,3-
diketones that are not easily accessible by known meth-
ods.9a–d To illustrate this, we hydrolyzed three of the
Table 2 Yields and Physical Data of Diketones 4
enaminones (3m–p) to the corresponding 1,3-diketones 4
(Scheme 1, Table 2). The hydrolysis was carried out with
15% aqueous H2SO4 for 1 hour at 70 °C (10 h at 55 °C for
3m). The synthesis of trichloroacetylacetone 4m was also
carried out as one-pot procedure starting from 2m.
4
Yield mp
(%) (°C)
1H NMR (ppm, Hz)
m
o
91
96
oil8a,b
2.3 (s, 3 H), 6.07 (s, 1 H), 13.47 (s, 1 H)
112–113a 2.27 (s, 3 H), 6.24 (s, 1 H), 8.03 (d, 2 H,
J = 8.7), 8.29 (d, 2 H, J = 8.7), 15.91 (s, 1 H)
In conclusion, the described synthetic procedure provides
a convenient two-step route to unsymmetrical -enamino
ketones 3, starting from symmetrical -enamino ketones
(1h–m) or -enamino amides (1d–f, n–p). An additional
step, involving acidic hydrolysis of the enamino ketones
p
95
43–45b
2.17 (s, 3 H), 6.03 (s, 1 H), 7.25–7.55 (m, 3 H),
15.67 (s, 1 H)
a Lit.9c 112.0 – 112.8 °C.
b Lit.9d 44 – 46 °C.
Synthesis 2003, No. 14, 2221–2225 © Thieme Stuttgart · New York

PAPER
Synthesis of Unsymmetrical -Enamino Ketones
2223
2b
Mp 58–60 °C.
3, affords unsymmetrical 1,3-diketones that are not readi-
ly available by classic methods.
1H NMR: = 1.31 (t, 3 H, J = 7.1 Hz), 2.06 (s, 3 H), 2.24 (s, 3 H),
2.86 (t, 2 H, J = 7.0 Hz), 3.50–3.57 (m, 2 H), 3.86 (s, 3 H) 3.88 (s,
3 H), 4.20 (q, 2 H, J = 7.1 Hz), 6.73–6.84 (m, 3 H), 12.55 (br, 1 H).
Melting points were determined on a Boetius hotstage apparatus
and are uncorrected. H NMR spectra were recorded on a Bruker
1
250 MHz device using CDCl3 as solvent. Chemical shifts ( , ppm)
are downfield from TMS as internal standard and coupling con-
stants are in Hz. All new compounds had elemental analyses within
0.4% of the theoretical values as well as correct parent ion peaks by
mass spectrometry. Petroleum had a bp 40–60 °C.
2c
Mp 93–95 °C.
1H NMR: = 0.67 (t, 3 H, J = 7.1 Hz), 2.33 (s, 3 H), 2.70 (t, 2 H,
J = 7.0 Hz), 3.21–3.29 (m, 2 H), 3.63 (q, 2 H, J = 7.1 Hz), 3.81 (s,
3 H), 3.85 (s, 3 H), 6.50–6.78 (m, 3 H), 7.02–7.06 (m, 2 H), 7.28–
7.38 (m, 3 H), 12.31 (br, 1 H).
Enaminones (1)
The starting enaminones were obtained in yields ranging from 75–
98%, according to the procedures published in reference,4 and novel
enmainones were characterized by their mp and 1H NMR spectra.
2d
Mp 124–126 °C.
1i
Oil.
1H NMR: = 1.40 (s, 3 H), 2.76 (t, 2 H, J = 7.1 Hz), 3.25–3.43 (m,
2 H), 3.86 (s, 3 H), 3.88 (s, 3 H), 6.56–6.81 (m, 3 H), 7.12–7.80 (m,
11 H), 11.75 (br, 1 H).
1H NMR: = 1.83 (s, 3 H), 2.01 (s, 3 H), 2.85 (t, 2 H, J = 7.0 Hz),
3.43–3.51 (m, 2 H), 5.01 (s, 1 H), 7.25–7.61 (m, 5 H), 10.85 (br,
1H).
2e
Mp 129–131 °C.
1j
1H NMR: = 2.00 (s, 3 H), 2.19 (s, 3 H), 2.84 (t, 2 H, J = 7.1 Hz),
3.46–3.54 (m, 2 H), 3.86 (s, 3 H), 3.88 (s, 3 H), 6.01 (br, 2 H), 6.74–
6.81 (m, 3 H), 11.92 (br, 1 H).
Mp 48–50 °C.
1H NMR: = 1.95 (s, 3 H), 2.12 (s, 3 H), 3.86 (s, 6 H), 4.43 (d, 2 H,
J = 6.0 Hz), 4.98 (s, 1 H), 6.73–6.84 (m, 3 H), 10.31 (br, 1 H).
2f
1k
Oil.
Mp 122–124 °C.
1H NMR: = 1.98 (s, 3 H), 2.15 (s, 3 H), 2.80 (t, 2 H, J = 7.1 Hz),
3.44–3.51 (m, 2 H), 3.84 (s, 3 H), 3.87 (s, 3 H), 6.70–6.81 (m, 3 H),
7.08–7.65 (m, 5 H), 8.14 (br, 1 H), 11.87 (br, 1 H).
1H NMR: = 1.98 (s, 3 H), 2.15 (s, 3 H), 4.53 (d, 2 H, J = 6.0 Hz),
5.10 (s, 1 H), 7.23–7.43 (m, 5 H), 10.59 (br, 1 H).
1l
Oil.
2g
Oil.
1H NMR: = 1.03 (t, 3 H, J = 7.2 Hz), 1.52–1.87 (m, 2 H), 2.09 (s,
3 H), 2.20 (s, 3 H), 3.35–3.48 (m, 2 H), 5.05 (s, 1 H), 10.56 (br, 1 H).
1H NMR: = 1.06 (t, 3 H, J = 7.1 Hz), 1.19 (t, 3 H, J = 7.1 Hz), 1.83
(s, 3 H), 2.03 (s, 3 H), 2.80–2.85 (m, 2 H), 3.27–3.53 (m, 6 H), 3.86
(s, 3H), 3.88 (s, 3 H), 6.73–6.84 (m, 3 H), 11.69 (br, 1 H).
1m
Oil.
2h
1H NMR: = 1.25 (t, 3 H, J = 7.3 Hz), 1.95 (s, 3 H), 2.02 (s, 3 H),
Mp 87–88 °C.
1H NMR: = 1.91 (s, 3 H), 2.17 (s, 3 H), 2.88 (t, 2 H, J = 6.8 Hz),
3.36–3.47 (m, 2 H), 5.08 (s, 1 H), 10.81 (br,1 H).
3.52–3.60 (m, 2 H), 3.87 (s, 6 H), 6.73–6.85 (m, 3 H), 12.05 (br, 1
H).
1n
Mp 90– 92 °C.
1H NMR: = 1.24 (t, 3 H, J = 7.3 Hz), 1.91 (s, 3 H), 3.30–3.45 (m,
2i
Mp 70–71 °C.
2 H), 4.50 (s, 1 H), 6.85 (br, 1 H), 7.19–7.69 (m, 5 H), 9.45 (br, 1 H).
1H NMR: = 1.88 (s, 3 H), 2.22 (s, 3 H), 2.95 (t, 2 H, J = 6.8 Hz),
3.56–3.70 (m, 2 H), 7.25–7.50 (m, 5 H), 12.03 (br, 1 H).
Acylated Enaminones 2; General Procedure
To a cooled (0–5 °C) and stirred solution of the corresponding
enaminone 1 (3 mmol) and Et3N (3 mmol) in CH2Cl2 (9 mL) was
added dropwise the corresponding acyl chloride (3 mmol). The re-
action mixture was allowed to warm to r.t. and the stirring continued
for the time shown in Table 1. For examples a, c, and d an addition-
al amount of Et3N (3 mmol) and acyl chloride (3 mmol) was added
after the second hour. The mixture was then washed with water (200
mL), dried (Na2SO4), and the solvent removed by distillation. The
product was purified by recrystallization or column chromatogra-
phy on neutral alumina with Et2O or Et2O –petroleum ether (1:1) as
eluent.
2j
Mp 85–87 °C.
1H NMR: = 2.10 (s, 3 H), 2.22 (s, 3 H), 3.88 (s, 6 H), 4.48 (d, 2 H,
J = 6.0 Hz), 6.78–-6.87 (m, 3 H), 12.19 (br, 1 H).
2k
Mp 70–72 °C.
1H NMR: = 2.08 (s, 3 H), 2.21 (s, 3 H), 4.55 (d, 2 H, J = 6.0 Hz),
7.25–7.41 (m, 5 H), 12.27 (br, 1 H).
2l
2a
Mp 48–50 °C.
Mp 55–57 °C.
1H NMR: = 1.05 (t, 3 H, J = 7.2 Hz), 1.53–1.89 (m, 2 H), 2.12 (s,
3 H), 2.22 (s, 3 H), 3.37–3.49 (m, 2 H), 11.97 (br, 1 H).
1H NMR: = 1.96 (s, 3 H), 2.26 (s, 6 H), 2.86 (t, 2 H, J = 7.0 Hz),
3.49–3.57 (m, 2 H), 3.86 (s, 3 H), 3.88 (s, 3 H), 6.74–6.85 (m, 3 H),
12.38 (br, 1 H).
Synthesis 2003, No. 14, 2221–2225 © Thieme Stuttgart · New York

2224
2m
A. P. Venkov, P. A. Angelov
PAPER
3l
Mp 83–85 °C.
Mp 52–53 °C (Lit.10 56 °C).
1H NMR: = 1.32 (t, 3 H, J = 7.3 Hz), 2.08 (s, 3 H), 2.19 (s, 3 H),
1H NMR: = 1.05 (t, 3 H, J = 7.2 Hz), 1.53–1.89 (m, 2 H), 2.15 (s,
3.33–3.44 (m, 2 H), 11.90 (br, 1 H).
3 H), 3.33–3.48 (m, 2 H), 5.80 (s, 1H), 10.70 (br,1H)
2n
3m
Mp 160–161 °C.
Mp 74–76 °C.
1H NMR: = 1.34 (t, 3 H, J = 7.3 Hz), 1.71 (s, 3 H), 3.29–3.39 (m,
1H NMR: = 1.32 (t, 3H, J = 7.3), 2.12 (s, 3 H), 3.35–3.46 (m, 2 H),
2 H), 7.01–7.65 (m, 10.5 H), 11.39 (br, 0.5 H), 12.16 (br, 1 H).
5.69 (s, 1 H), 10.69 (br, 1 H).
2o
3n
Mp 152–154 °C.
Oil.
1H NMR: = 1.37 (t, 3 H, J = 7.3 Hz), 1.81 (s, 3 H), 3.37–3.46 (m,
2 H), 7.03–7.31 (m, 5 H), 7.48 (br, 0.5 H), 7.78 (d, 2 H, J = 8.7 Hz),
8.23 (d, 2 H, J = 8.7 Hz), 11.36 (br, 0.5 H), 12.41 (br, 1 H).
1H NMR: = 1.33 (t, 3 H, J = 7.3 Hz), 2.09 (s, 3 H), 3.35–3.49 (m,
2 H), 5.65 (s, 1 H), 7.45–8.15 (m, 5 H), 9.93 (br,1 H).
3o
2p
Mp 94–95 °C.
Mp 142–144 °C.
1H NMR: = 1.35 (t, 3 H, J = 7.3 Hz), 1.87 (s, 3 H), 3.37–3.49 (m,
2 H), 7.02–7.57 (m, 8.5 H), 11.80 (br, 0.5 H), 12.60 (br, 1 H).
1H NMR: = 1.35 (t, 3 H, J = 7.3 Hz), 2.12 (s, 3 H), 3.37–3.48 (m,
2 H), 5.57 (s, 1 H), 7.98 (d, 2 H, J = 8.7 Hz), 8.23 (d, 2 H, J = 8.7),
11.57 (br, 1 H).
Enaminones 3; General Procedure
3p
TFA (3 mL) or phosphoric acid7 (12 g), as indicated in Table 1, was
added to the corresponding compound 2 (3 mmol) and the mixture
was vigorously stirred under the conditions indicated in Table 1.
Then, water (200 mL) was added and the mixture was extracted
with CH2Cl2 (3 × 20 mL). The combined extract was dried
(Na2SO4), and the solvent distilled off. The products were purified
by recrystallization or column chromatography on neutral alumina
using Et2O–petroleum ether (1:4) as eluent.
Oil.
1H NMR: = 1.33 (t, 3 H, J = 7.3 Hz), 2.10 (s, 3 H), 3.36–3.49 (m,
2 H), 5.37 (s, 1 H), 7.30–7.63 (m, 3 H), 11.39 (br, 1 H)
1,3-Diketones (4); General Procedure
H2SO4 (15% aq, 30 mL) was added to the corresponding enaminone
3 (5 mmol) and the mixture was vigorously stirred for 1 h at 65–
70 °C (10 h at 55 °C for 3m). Water (200 mL) was added and the
mixture was extracted with CH2Cl2 (3 × 20 mL). The combined ex-
tract was dried (Na2SO4) and the solvent distilled off. The products
were purified by recrystallization or column chromatography on
neutral alumina using Et2O–petroleum ether (1:4) as eluent.
3d
Oil.
1H NMR: = 2.07 (s, 3 H), 2.71 (t, 2 H, J = 7.0 Hz), 3.29–3.37 (m,
2 H), 3.80 (s, 3 H), 3.85 (s,3 H), 4.99 (s,1 H), 6.54–6.77 (m, 3 H),
7.11–7.15 (m, 2 H), 7.26–7.36 (m, 3 H), 10.82 (br, 1 H).
Trichloroacetylacetone 4m
The acylated enaminone 2m (5 mmol) was dissolved in concd
H2SO4 (3 mL) and the solution was stirred for 1 h at r.t. Then water
(30 mL) was added and the mixture was vigorously stirred for 10 h
at 55 °C. The reaction mixture was worked up as described above.
3e–g
Mp 37–40 °C.
1H NMR: = 1.75 (s, 3 H), 1.99 (s, 3 H), 2.80 (t, 2 H, J = 6.9 Hz),
3.41–3.49 (m, 2 H), 3.86 (s, 6 H), 4.92 (s, 1 H), 6.71–6.84 (m, 3 H),
10.92 (br, 1 H).
Acknowledgment
3h
We acknowledge financial support from the Fund for scientific re-
search of the Plovdiv University.
Mp 72–73 °C.
1H NMR: = 1.91 (s, 3 H), 2.87 (t, 2 H, J = 6.8 Hz), 3.53–3.61 (m,
2 H), 3.87 (s, 6 H), 5.64 (s, 1 H), 6.72–6.85 (m, 3 H), 10.83 (br, 1 H).
References
3i
Oil.
(1) Dr Atanas Venkov passed away suddenly on July 21st, 2003,
aged 62.
1H NMR: = 1.95 (s, 3 H), 2.91 (t, 2H, J = 6.8 Hz), 3.55–3.69 (m,
2 H), 5.75 (s, 1 H), 7.25–7.50 (m, 5 H), 10.89 (br, 1 H).
(2) (a) Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277. (b) Lue,
P.; Greenhill, J. V. Adv. Heterocycl. Chem. 1996, 67, 207.
(c) Michael, J. P.; De Koning, C. B.; Gravestock, D.;
Hosken, G. D.; Howard, A. S.; Jungmann, C. M.; Krause, R.
W. M.; Parsons, A. S.; Pelly, S. C.; Stanbury, T. V. Pure
Appl. Chem. 1999, 71, 979. (d) Katritzky, A. R.; Barcock,
R. A.; Long, Q. H.; Balasubramanian, M.; Malhotra, N.;
Greenhill, J. V. Synthesis 1993, 233.
3j
Mp 94–95 °C.
1H NMR: = 2.15 (s, 3 H), 3.88 (s, 6 H), 4.48 (d, 2 H, J = 6.0 Hz),
5.74 (s, 1 H), 6.79–6.88 (m, 3 H), 10.87 (br, 1 H).
(3) (a) Bartoli, G.; Cimarelli, C.; Palmieri, G.; Bosco, M.;
Dalpozzo, R. Synthesis 1990, 895. (b) Katritzky, A. R.;
Fang, Y.; Donkor, A.; Xu, J. Synthesis 2000, 2029.
(4) Venkov, A. P.; Angelov, P. A. Synth. Commun. 2003, 33,
3025.
3k
Mp 93–94 °C (Lit.9a,10 93 °C).
1H NMR: = 2.14 (s, 3 H), 4.55 (d, 2 H, J = 6.0 Hz), 5.75 (s, 1 H),
7.26–7.39 (m, 5 H), 10.93 (br, 1 H).
Synthesis 2003, No. 14, 2221–2225 © Thieme Stuttgart · New York

PAPER
(5) (a) Tietze, L. F.; Wichmann, J. Chem. Ber. 1992, 2571.
Synthesis of Unsymmetrical -Enamino Ketones
2225
(8) (a) Dudek, G. O.; Volpp, G. P. J. Am. Chem. Soc. 1963,
2697. (b) Dudek, G. O.; Holm, R. H. J. Am. Chem. Soc.
1962, 2691.
(b) Tietze, L. F.; Wichmann, J. Liebigs Ann. Chem. 1992,
1063.
(6) (a) Kozerski, L. Tetrahedron 1976, 1299. (b) Alt, G. H.;
Speziale, A. J. J. Org. Chem. 1964, 798. (c) Burgemeister,
T.; Dannhardt, G.; Eibler, E.; Paulus, B.; Ziereis, K. Arch.
Pharm. (Weinheim, Ger.) 1988, 345.
(7) The phosphoric acid used in these experiments was obtained
by adding P2O5 (39.4 g) to 85% H3PO4 (d = 1.7, 58.82 mL/
100 g).
(9) (a) Ringel, C.; Mayer, R. J. Prakt. Chem. 1964, 333.
(b) Morris, M. L.; Koob, R. D. Org. Mass Spectrom. 1982,
17, 503. (c) Walker, H. G.; Hauser, C. W. J. Am. Chem. Soc.
1946, 68, 2742. (d) Hoehn, H. US Patent 4273776, 1981.
(10) Boehme, H.; Traenka, M. Z. Chem. 1985, 25, 21.
Synthesis 2003, No. 14, 2221–2225 © Thieme Stuttgart · New York